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Exploring the benefits of Resveratrol in managing endometriosis.

Resveratrol: Unveiling Nature's Anti-Inflammatory and Antioxidant Elixir

March 25, 2024 Nadera Mansouri-Attia

Endometriosis, a chronic and often painful condition affecting millions of women worldwide, poses significant challenges to those affected and their healthcare providers. While conventional treatments focus on symptom management, emerging research suggests that certain dietary supplements such as antioxidant may offer promising avenues for alleviating the symptoms and promote fertility. In this blog post, we explore a key dietary supplement—Resveratrol—and its potential benefits in helping manage this complex condition.

Resveratrol: Unveiling Nature’s Anti-Inflammatory and Antioxidant Elixir

What is Resveratrol?

Resveratrol, a polyphenolic compound found in the skin of red grapes and berries, as well as in red wine, has garnered attention for its potent anti-inflammatory and antioxidant properties. Research has shown that this natural compound holds immense therapeutic potential in combating various health conditions, including endometriosis.

Is it Safe?

Yes, resveratrol is generally regarded as safe when consumed within recommended doses.

Recommended Dosage and Mechanisms of Action

Studies suggest that doses of up to 50 mg of resveratrol may be beneficial. In the context of endometriosis, resveratrol’s actions are multifaceted1:

  • Activation of SIRT1 Receptor: Resveratrol activates the SIRT1 receptor, which plays a pivotal role in ovarian function2 by promoting mitochondrial biogenesis (powerhouse of a cell)3, regulating oxidative stress levels in oocyte and granulosa cells and activating the production of progesterone.
  • Mitigation of Oxidative Stress: By modulating the sirtuin pathway4, resveratrol helps reduce oxidative stress in oocytes and granulosa cells, thereby protecting against DNA damage and promoting oocyte maturation.
  • Anti-Inflammatory Effects: Resveratrol suppresses pro-inflammatory pathways, including the NF-κB pathway5 and the synthesis of COX enzymes involved in prostaglandin production6 (which fuels the production of estrogen) thus reducing inflammation associated with endometriosis.

Evidence-Based Insights

A study highlighted in Nature Scientific Report7 uncovered that infertility stemming from endometriosis might originate from DNA damage in oocytes (eggs), caused by oxidative stress. Crucially, the research indicates that this DNA damage, primarily attributed to oxidative stress, can be counteracted with antioxidants like melatonin and resveratrol. This intervention has the potential to restore the oocyte, facilitating its progression and maturation into an egg capable of fertilization.
In this study, the researchers investigated the impact of oxidative stress on the development of oocytes by subjecting immature, healthy mouse oocytes to follicular fluid from women with endometriosis (ENDO-FF) in vitro. They observed the development of these oocytes in comparison with those cultured in follicular fluid from healthy women (control group without endometriosis).

The findings revealed that exposure to Endo-FF resulted in:

  • increased levels of reactive oxygen species (ROS) in the mouse oocytes,
  • greater DNA damage within the mouse oocytes,
  • a reduction or delay in oocyte maturation relative to the control group.

The study found that the maturation process of oocytes was hindered by Endo-FF, with development ceasing at a critical phase (metaphase I arrest). This stage is notable for the activation of a specific DNA damage sensor (Spindle Assembly Checkpoint/DNA Damage Response), which evaluates DNA integrity and halts oocyte maturation by triggering a protein (ATM kinase). The research indicated that ROS directly stimulates this protein, thereby stopping oocyte development.

Additionally, the study demonstrated that the adverse effects on oocyte maturation could be mitigated by reducing ROS levels using antioxidants like resveratrol and melatonin in the culture medium.

The study underscores the significant detrimental effects of ROS and pro-inflammatory factors found in the follicular fluid of patients with endometriosis on oocyte development. These effects are likely more pronounced in the human ovary, where oocytes are exposed to follicular fluid at higher concentrations and for longer durations than those in this study. Consequently, the pathway is particularly vulnerable to diseases such as endometriosis and potentially other conditions that increase ROS levels, including polycystic ovary syndrome (PCOS).

Other studies have focused on resveratrol benefits as it relates to pain associated with endometriosis.

A study8 presented encouraging outcomes when resveratrol was added to an oral contraceptive regimen containing drosperidone over a two-month period. The results showed significant pain reduction, with 82% of participants experiencing total relief from pelvic pain and dysmenorrhea.
Nevertheless, other studies9-10 did not demonstrate any reduction in pain measurements between the treated and control groups.

In conclusion, dietary supplements such as resveratrol offer promising avenues for women with endometriosis. By targeting inflammation, oxidative stress, and cellular dysfunction, this natural compound may complement conventional treatments and improve outcomes for those affected by this challenging condition. However, it’s crucial to consult with healthcare professionals before incorporating dietary supplements into your regimen, ensuring safety and efficacy.

References

  1. Baur, J.A.; Sinclair, D.A. Therapeutic potential of resveratrol: The in vivo evidence. Nat. Rev. Drug Discov. 2006, 5, 493–506.
  2. Ortega I, Duleba AJ. Ovarian actions of resveratrol. Ann N Y Acad Sci. 2015 Aug;1348(1):86-96. doi: 10.1111/nyas.12875. PMID: 26315293.
  3. Civitarese AE, Smith SR, Ravussin E. Diet, energy metabolism and mitochondrial biogenesis. Curr Opin Clin Nutr Metab Care. 2007 Nov;10(6):679-87.
  4. Taguchi, A.; Wada-Hiraike, O.; Kawana, K.; Koga, K.; Yamashita, A.; Shirane, A.; Urata, Y.; Kozuma, S.; Osuga, Y.; Fujii, T. Resveratrol suppresses inflammatory responses in endometrial stromal cells derived from endometriosis: A possible role of the sirtuin 1 pathway. J. Obstet. Gynaecol. Res. 2014, 40, 770–778.
  5. Bruner-Tran, K.L.; Osteen, K.G.; Taylor, H.S.; Sokalska, A.; Haines, K.; Duleba, A.J. Resveratrol inhibits development of experimental endometriosis in vivo and reduces endometrial stromal cell invasiveness in vitro. Biol. Reprod. 2011, 84, 106–112.
  6. Cenksoy, P.O.; Oktem, M.; Erdem, O.; Karakaya, C.; Cenksoy, C.; Erdem, A.; Guner, H.; Karabacak, O. A potential novel treatment strategy: Inhibition of angiogenesis and inflammation by resveratrol for regression of endometriosis in an experimental rat model. Gynecol. Endocrinol. 2015, 31, 219–224.
  7. Hamdan M, Jones KT, Cheong Y, Lane SI. The sensitivity of the DNA damage checkpoint prevents oocyte maturation in endometriosis. Sci Rep. 2016 Nov 14; 6:36994.
  8. Maia H, Haddad C, Pinheiro N, et al. Advantages of the association of resveratrol with oral contraceptives for management of endometriosis-related pain. Int J Womens Health. 2012; 4: 543–549.
  9. Mendes da Silva D, Gross LA, Neto Ed, et al. The Use of Resveratrol as an Adjuvant Treatment of Pain in Endometriosis: A Randomized Clinical Trial. J Endocr Soc. 2017; 1(4]: 359–369.
  10. Nodler JL, DiVasta AD, Vitonis AF, et al. Supplementation with vitamin D or ω-3 fatty acids in adolescent girls and young women with endometriosis (SAGE]: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr. 2020; 112(1]:229–236.
  11. Crane FL. Biochemical functions of coenzyme Q10. J Am Coll Nutr. 2001 Dec;20(6):591-8.
  12. Quinzii CM, López LC, Gilkerson RW, Dorado B, Coku J, Naini AB, Lagier-Tourenne C, Schuelke M, Salviati L, Carrozzo R, Santorelli F, Rahman S, Tazir M, Koenig M, DiMauro S, Hirano M. Reactive oxygen species, oxidative stress, and cell death correlate with level of CoQ10 deficiency. FASEB J. 2010 Oct;24(10):3733-43.